scholarly journals Impairment of IKCa channels contributes to uteroplacental endothelial dysfunction in rat diabetic pregnancy

2015 ◽  
Vol 309 (4) ◽  
pp. H592-H604 ◽  
Author(s):  
Natalia I. Gokina ◽  
Adrian D. Bonev ◽  
Julie Phillips ◽  
Alexander P. Gokin ◽  
Kelsey Veilleux ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Membrane Potential ◽  
Endothelial Dysfunction ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Dysfunction ◽  
Citrate Buffer ◽  
Pregnant Rats ◽  
Intracellular Ca ◽  
The Impact

Diabetes in rat pregnancy is associated with impaired vasodilation of the maternal uteroplacental vasculature. In the present study, we explored the role of endothelial cell (EC) Ca2+-activated K+ channels of small conductance (SKCa channels) and intermediate conductance (IKCa channels) in diabetes-induced uterine vascular dysfunction. Diabetes was induced by injection of streptozotocin to second-day pregnant rats and confirmed by the development of maternal hyperglycemia. Control rats were injected with citrate buffer. Changes in smooth muscle cell intracellular Ca2+ concentration, membrane potential, and vasodilation induced by SKCa/IKCa channel activators were studied in uteroplacental arteries of control and diabetic rats. The impact of diabetes on SKCa- and IKCa-mediated currents was explored in freshly dissociated ECs. NS309 evoked a potent vasodilation that was effectively inhibited by TRAM-34 but not by apamin. NS309-induced smooth muscle cell intracellular Ca2+ concentration, membrane potential, and dilator responses were significantly diminished by diabetes; N-cyclohexyl- N-2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-4-pyrimidinamine (CyPPA)-evoked responses were not affected. Ca2+-activated ion currents in ECs were insensitive to paxilline, markedly inhibited by charybdotoxin (ChTX), and diminished by apamin. NS309-induced EC currents were generated mostly due to activation of ChTX-sensitive channels. Maternal diabetes resulted in a significant reduction in ChTX-sensitive currents with no effect on apamin-sensitive or CyPPA-induced currents. We concluded that IKCa channels play a prevalent role over SKCa channels in the generation of endothelial K+ currents and vasodilation of uteroplacental arteries. Impaired function of IKCa channels importantly contributes to diabetes-induced uterine endothelial dysfunction. Therapeutic restoration of IKCa channel function may be a novel strategy for improvement of maternal uteroplacental blood flow in pregnancies complicated by diabetes.

scholarly journals Smooth Muscle Cell–Specific Disruption of the BBSome Causes Vascular Dysfunction

Hypertension ◽  
2019 ◽  
Vol 74 (4) ◽  
pp. 817-825 ◽  
Author(s):  
John J. Reho ◽  
Deng-Fu Guo ◽  
Donald A. Morgan ◽  
Kamal Rahmouni
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Dysfunction

A synthetic transmembrane segment derived from TRPV4 channel self-assembles into potassium-like channels to regulate vascular smooth muscle cell membrane potential

2014 ◽  
Vol 2 (24) ◽  
pp. 3809-3818 ◽  
Author(s):  
Zhiqiang Yu ◽  
Jie Li ◽  
Jinhang Zhu ◽  
Min Zhu ◽  
Feifei Jiang ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Membrane Potential ◽  
Cell Membrane ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Smooth Muscle Cell ◽  
Cell Membrane Potential ◽  
Trpv4 Channel ◽  
Muscle Cell Membrane

A synthetic K+-like channel mediates K+outward flow to regulate vascular smooth muscle cell membrane potential, blood vessel tone and blood pressure.

Chronic intrauterine pulmonary hypertension compromises fetal pulmonary artery smooth muscle cell O2 sensing

2003 ◽  
Vol 285 (6) ◽  
pp. L1354-L1361 ◽  
Author(s):  
Bradley C. Linden ◽  
Ernesto R. Resnik ◽  
Kristine J. Hendrickson ◽  
Jean M. Herron ◽  
Timothy J. O'Connor ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Smooth Muscle ◽  
Pulmonary Artery ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Ductus Arteriosus ◽  
Intracellular Ca ◽  
Acute Increase ◽  
Pulmonary Artery Smooth Muscle ◽  
O2 Sensing

To test the hypothesis that chronic intrauterine pulmonary hypertension (PHTN) compromises pulmonary artery (PA) smooth muscle cell (SMC) O2 sensing, fluorescence microscopy was used to study the effect of an acute increase in Po2 on the cytosolic Ca2+ concentration ([Ca2+]i) of chronically hypoxic subconfluent monolayers of PA SMC in primary culture. PA SMCs were derived from fetal lambs with PHTN due to intrauterine ligation of the ductus arteriosus. Acute normoxia decreased [Ca2+]i in control but not PHTN PA SMC. In control PA SMC, [Ca2+]i increased after Ca2+-sensitive (KCa) and voltage-sensitive (Kv) K+ channel blockade and decreased after diltiazem treatment. In PHTN PA SMC, KCa blockade had no effect, whereas Kv blockade and diltiazem increased [Ca2+]i. Inhibition of sarcoplasmic reticulum Ca2+ ATPase activity caused a greater increase in [Ca2+]i in controls compared with PHTN PA SMC. Conversely, ryanodine caused a greater increase of [Ca2+]i in PHTN compared with control PA SMC. KCa channel mRNA is decreased and Kv channel mRNA is unchanged in PHTN PA SMC compared with controls. We conclude that PHTN compromises PA SMC O2 sensing, alters intracellular Ca2+ homeostasis, and changes the predominant ion channel that determines basal [Ca2+]i from KCa to Kv.

scholarly journals Pleiotropic actions of factor Xa inhibition in cardiovascular prevention: mechanistic insights and implications for anti-thrombotic treatment

2020 ◽  
Author(s):  
Hugo ten Cate ◽  
Tomasz J Guzik ◽  
John Eikelboom ◽  
Henri M H Spronk
Keyword(s):  
Smooth Muscle ◽  
Endothelial Dysfunction ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Cell Activation ◽  
Vascular Inflammation ◽  
Factor Xa ◽  
Cardiovascular Prevention ◽  
Physiological Conditions

Abstract Atherosclerosis is a chronic inflammatory disease in which atherothrombotic complications lead to cardiovascular morbidity and mortality. At advanced stages, myocardial infarction, ischaemic stroke, and peripheral artery disease, including major adverse limb events, are caused either by acute occlusive atherothrombosis or by thromboembolism. Endothelial dysfunction, vascular smooth muscle cell activation, and vascular inflammation are essential in the development of acute cardiovascular events. Effects of the coagulation system on vascular biology extend beyond thrombosis. Under physiological conditions, coagulation proteases in blood are pivotal in maintaining haemostasis and vascular integrity. Under pathological conditions, including atherosclerosis, the same coagulation proteases (including factor Xa, factor VIIa, and thrombin) become drivers of atherothrombosis, working in concert with platelets and vessel wall components. While initially atherothrombosis was attributed primarily to platelets, recent advances indicate the critical role of fibrin clot and plasma coagulation factors. Mechanisms of atherothrombosis and hypercoagulability vary depending on plaque erosion or plaque rupture. In addition to contributing to thrombus formation, factor Xa and thrombin can affect endothelial dysfunction, oxidative stress, vascular smooth muscle cell function as well as immune cell activation and vascular inflammation. By these mechanisms, they promote atherosclerosis and contribute to plaque instability. In this review, we first discuss the postulated vasoprotective mechanisms of protease-activated receptor signalling induced by coagulation enzymes under physiological conditions. Next, we discuss preclinical studies linking coagulation with endothelial cell dysfunction, thromboinflammation, and atherogenesis. Understanding these mechanisms is pivotal for the introduction of novel strategies in cardiovascular prevention and therapy. We therefore translate these findings to clinical studies of direct oral anticoagulant drugs and discuss the potential relevance of dual pathway inhibition for atherothrombosis prevention and vascular protection.

Isoflurane Alters Angiotensin II–Induced Ca2+Mobilization in Aortic Smooth Muscle Cells from Hypertensive Rats

2002 ◽  
Vol 97 (3) ◽  
pp. 642-651 ◽  
Author(s):  
Emmanuel Samain ◽  
Hélène Bouillier ◽  
Catherine Rucker-Martin ◽  
Jean-Xavier Mazoit ◽  
Jean Marty ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Smooth Muscle Cell ◽  
Spontaneously Hypertensive Rats ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Intracellular Ca ◽  
Wistar Kyoto

Background Angiotensin II (AngII) is a potent vasoconstrictor involved in the short-term control of arterial blood pressure. Isoflurane was reported to decrease vascular tone through an alteration of vascular smooth muscle cell vasomotor response to several agonists, but its effect on AngII signaling is not known. On the other hand, vascular response to AngII is altered in hypertension. In this study, the authors tested the hypothesis that (1) isoflurane alters AngII-induced intracellular Ca mobilization in aortic vascular smooth muscle cell from Wistar Kyoto and spontaneously hypertensive rats, and (2) this effect could be associated with an alteration of the organization of microtubular network, reported to be involved in AngII signaling. Methods The effect of 0.5-3% isoflurane was studied (1) on AngII (10 m)-induced intracellular Ca mobilization, intracellular Ca release from internal stores, and Ca influx in Fura-2 loaded cultured aortic vascular smooth muscle cell isolated from 6-week-old Wistar Kyoto and spontaneously hypertensive rats, using fluorescent imaging microscopy; and (2) on the organization of cytoskeletal elements, using immunofluorescence labeling. Results In both stains, isoflurane decreased in a concentration-dependent manner AngII-induced intracellular Ca mobilization, Ca release from internal stores, and Ca influx through nifedipine-insensitive Ca channels. This effect occurred at a lower concentrations of isoflurane in Wistar Kyoto rats than in spontaneously hypertensive rats. In both strains, the effect of isoflurane on AngII- Ca mobilization was abolished by impairment with nocodazole, vinblastine, or paclitaxel of microtubules polymerization. Isoflurane directly altered tubular network organization in a concentration-dependent and reversible manner. Conclusions Isoflurane decreased AngII-induced Ca mobilization at clinically relevant concentrations, suggesting that vascular response to AngII could be altered during isoflurane anesthesia. The hypertensive strain was found less sensitive than the normotensive one. In both strains, the isoflurane effect was associated with a microtubular network interaction.

scholarly journals Mathematical model of excitation-contraction in a uterine smooth muscle cell

Physiome ◽  
2021 ◽  
Author(s):  
Weiwei Ai ◽  
Limor Freifeld ◽  
David Nickerson
Keyword(s):  
Mathematical Model ◽  
Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Myosin Light Chain ◽  
Original Data ◽  
Uterine Smooth Muscle ◽  
Intracellular Ca ◽  
Myometrial Smooth Muscle Cell ◽  
Mlc Phosphorylation

The Bursztyn et al. (2007) paper proposes a mathematical model of excitation-contraction in a myometrial smooth muscle cell (SMC). The model incorporates processes of intracellular Ca^2+ concentration control, myosin light chain (MLC) phosphorylation and stress production. We create a modularized CellML implementation of the model, which is able to simulate these processes against the original data.

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